Regulation of CD4 and CD8 coreceptor expression and CD4 versus CD8 lineage decisions

During blood cell development, hematopoietic stem cells generate diverse mature populations via several rounds of binary fate decisions. At each bifurcation, precursors adopt one fate and inactivate the alternative fate either stochastically or in response to extrinsic stimuli and stably maintain the selected fates. Studying of these processes would contribute to better understanding of etiology of immunodeficiency and leukemia, which are caused by abnormal gene regulation during the development of hematopoietic cells. The CD4(+) helper versus CD8(+) cytotoxic T-cell fate decision serves as an excellent model to study binary fate decision processes. These two cell types are derived from common precursors in the thymus. Positive selection of their TCRs by self-peptide presented on either MHC class I or class II triggers their fate decisions along with mutually exclusive retention and silencing of two coreceptors, CD4 and CD8. In the past few decades, extensive effort has been made to understand the T-cell fate decision processes by studying regulation of genes encoding the coreceptors and selection processes. These studies have identified several key transcription factors and gene regulatory networks. In this chapter, I will discuss recent advances in our understanding of the binary cell fate decision processes of T cells.